Enteric bacteria have related house keeping genes in about the same chromosomal order. The DNA differences between say Salmonella and E. coli appear to be sequences which are clustered together within islands of non-homologous DNA. These islands appear to contain most of the genes that are involved in pathogenesis and have been called pathogenicity islands although their origin, means of transmission, and precisely what they contain remain a mystery. There are two major aims in this proposal. One is to identify the loops or islands that distinguish various Salmonella (with different host preferences) from each other, from E. coli, and from other enteric bacteria. Also part of this aim is to construct Salmonella derivatives missing the islands or containing mutations in the islands and then characterize the phenotype of the derivative strains by a variety of virulence assays. The second major aim is to determine the role of genetic rearrangement in S. Typhi, if any. S. typhi and some S. Paratyphi can cause typhiod fever. The authors observed that these human adapted strains undergo genetic rearrangement at high frequency. In culture the same kinds of rearrangements have never been observed. The authors believe that the rearrangements are associated with growth in cells and will investigate this hypothesis.